FIGURE 8.

Model whereby integrin α1β1 protects against severe hepatic insulin resistance while promoting TG accumulation. Integrin α1 protein expression increases when wild-type mice are fed a HF diet. This leads to increased integrin α1β1 cell signaling upon collagen binding. Upon insulin stimulation, the combination of both insulin and integrin α1β1 signaling leads to the phosphorylation and subsequent activation of IRS1 and Akt. This results in the partial suppression of hepatic glucose output. Circulating FFAs are taken up by the liver and utilized primarily for the synthesis of DAG and TG, while some may be shunted toward the mitochondria for mitochondrial (mt) respiration. In contrast, when integrin α1-null mice are fed a HF diet and insulin levels are high, the absence of integrin signaling leads to decreased IRS1 and Akt activation. This results in no suppression of hepatic glucose output. Circulating FFAs are lower, and the available FFAs are utilized primarily by the mitochondria for mitochondrial respiration. This results in decreased DAG and TG levels.